Apparatus and method for monitoring a vascular access of a patient subjected to an extracorporeal blood treatment

ABSTRACT

In the apparatus and method for monitoring a vascular access ( 6 ) of an extracorporeal circuit ( 5; 10 ) of a patient, a control and calculation unit ( 17 ) varies a flow rate of a blood pump ( 9 ) predisposed to cause blood to circulate in the extracorporeal circuit. The control and calculation unit receives the pressure values in the blood withdrawal line ( 5 ) and the blood return line ( 10 ) from two pressure sensors ( 8, 12 ); the pressure values are a series of different values of the blood flow rate. The control and calculation unit processes the data gathered by means of a mathematical model which describes the variation of pressure in the vascular access as a function of the flow rate, in order to determine the blood flow rate in the vascular access. The invention detects the presence and location of a stenosis at the vascular access of a patient subjected to a hemodialysis treatment.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the priority of Italian Patent Application No. M02003 A 000018, filed on Jan. 28, 2003, and the benefit of U.S. Provisional Application No. 60/466,052, filed on Apr. 29, 2003, the contents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The invention relates to a system for monitoring vascular access in a patient undergoing extracorporeal blood treatment.

Specifically, though not exclusively, the invention can be usefully applied in the field of extracorporeal treatment for kidney failure.

Setting up an extracorporeal blood treatment, such as for example hemodialysis therapy, requires blood circulation in an extracorporeal circuit connected to the cardiovascular circuit of the patient through a vascular access.

The blood, taken from the patient and sent through an extracorporeal circuit, is subjected to a treatment, generally passing through a treatment unit (for example a dialyzer filter) and thereafter returned to the patient. The vascular access is where the blood is removed from the cardio-vascular system of the patient and returned to the system.

One of the vascular accesses most commonly used in hemodialysis therapy is the Cimino-Brescia artero-venous fistula access. Other vascular access types are known, however. For reasons of simplicity the present description will make reference to the artero-venous fistula as an example of vascular access, without excluding other types of vascular access from the claimed field of protection.

In an extracorporeal treatment the blood is usually taken from the vascular access by an arterial needle fluidly connected to the extracorporeal circuit. After having passed through the treatment unit, the blood is sent back to the vascular access through a venous needle. Generally blood circulation in the extracorporeal circuit is performed by a positive displacement pump, generally peristaltic.

One of the problems of extracorporeal blood treatment is monitoring the efficiency of the vascular access.

A parameter indicative of this efficiency is the blood flow rate which the vascular access can supply. This flow rate is usually greater than the blood flow rate through the extracorporeal circuit. For example, in normal conditions the blood flow rate at the vascular access is about 800÷1200 ml/minute, while the blood flow rate in the extracorporeal circuit varies between 100 and 700 ml/minute.

The flow rate at the vascular access can diminish due to a vascular pathology, such as, for example, a stenosis, i.e. a narrowing of the blood passage section, or for example due to a drop in cardiac output. The presence and location of a stenosis at the vascular access should be determined as soon as possible in order to prevent the stenosis degenerating into a thrombosis (occlusion of the blood vessels).

A reduced-efficiency vascular access can lead to the undesirable phenomenon of recirculation of blood during treatment. Recirculation consists in the presence during treatment of blood flow proceeding in an opposite to the desired direction, i.e. from the return zone of the treated blood (venous needle) to the supply zone of the blood to be treated (arterial needle). Flow recirculation therefore consists in return (in the extracorporeal circuit) of blood which has already been subjected to treatment, with a consequent diminution in treatment efficiency.

Various systems have been proposed for monitoring vascular access and, more generally, the cardiovascular system of a patient subjected to extracorporeal blood treatment.

EP 1 044 695 A2 teaches a method for determining the blood flow rate in a vascular access during hemodialysis treatment. The method varies the blood flow rate of the extracorporeal circuit and measures the arterial and venous pressures in the extracorporeal circuit during the above-cited flow rate variations. The operations are carried out in two different conditions: first with the vascular access open, in which a part of the blood flow passes through the vascular access between the withdrawal needle and the return needle, and then when the vascular access is closed, in which the vascular access flow between withdrawal needle and return needle is zero. According to the method of EP 1 044 695 A2, vascular access blood flow rate, with the vascular access open, is judged to be equal to the blood pump flow rate at which the difference of arterial pressure (or venous pressure) in the two different situations is zero.

This method has the drawback that it is necessary to intervene mechanically on the fistula to interrupt blood flow.

WO 00/18451 teaches a method for determining the flow in a fistula of a patient using an extracorporeal blood flow circuit, such as for example a hemodialysis circuit, in which the blood flows from a withdrawal point in the fistula to a return point in the fistula. The method varies the blood flow rate in the extracorporeal circuit and takes a reading of a signal which can be correlated with the fistula flow rate downstream of the withdrawal point. The blood flow rate upstream of the withdrawal point is evaluated at equal the blood flow rate obtaining in the extracorporeal circuit when the fistula blood flow rate downstream, read with the above-described signal, is zero. WO 00/18451 includes an embodiment in which the signal which can be correlated to the fistula blood flow downstream of the withdrawal point is generated by an ultrasonic sensor which operates directly on the patient's vascular access.

The use of a sensor to directly measure the blood flow rate in the fistula tract comprised between the withdrawal needle and the return needle leads to a certain constructional complication, as well as some discomfort for the patient.

EP 1 020 199 A2 teaches a method for detecting the presence of a stenosis in a vascular access during extracorporeal blood treatment. The method includes the use of at least one pressure sensor predisposed in the extracorporeal circuit along the arterial line upstream of the blood pump. A stenosis can be calculated from the entity of the pressure pulse measured by the pressure sensor.

A pressure sensor can be placed on the arterial line too downstream of the blood pump and upstream of a dialyzer, and a further pressure sensor can be placed on the venous line downstream of the dialyzer. The method also includes a reading of the pressure pulse frequency and use of that frequency as a signal entity correction factor. The pressure pulse frequency signal can be corrected by means of a function depending on the blood pump flow rate.

The data deductible from the method described in EP 1 020 199 A2 is however limited: in particular, the method provides only a general indication of the hemodynamic state of the fistula, signalling the presence of a stenosis, but it cannot gather more detailed data, such as for example the vascular access blood flow rate or the location of any stenoses found.

U.S. Pat. No. 5,830,365 teaches a method for determining some hemodynamic parameters, among which the blood flow rate in a fistula during an extracorporeal blood treatment. The method involves the alteration of at least one chemical-physical characteristic of the blood in the venous line of the extracorporeal circuit, and recording the change which occurs in the arterial line following this alteration. The alteration can be a change in the concentration of an indicator, or a change in the temperature or pressure. In a specific embodiment use is made of a hemodialysis machine provided with a dialyzer where a dialysis solution containing an indicator flows and the concentration change of the indicator in the venous and arterial lines of the extracorporeal circuit connected to the dialyzer is registered. In the venous line the concentration of the indicator increases by effect of back-filtration through the dialyzer. In the arterial line the concentration of the indicator increases by effect of recirculation in the fistula. The change of concentration in the arterial and venous lines is read by ultrasonic sensors. Alteration (in this case the change in concentration) is performed in two stages: first when the blood flows in the normal direction through the extracorporeal circuit, then when the blood flows in the opposite direction. The method includes the use of a device for inverting the blood flow direction in the extracorporeal circuit. According to the method taught in U.S. Pat. No. 5,830,365 the change in concentration measured in the first stage enables calculation of recirculation at normal flow rate, while the change in concentration measured in the second stage enables calculation of recirculation when the flow is inverted. The two calculated values thus enable a calculation of various hemodynamic parameters among which the blood flow rate in the fistula.

However the alteration of the chemical-physical properties of the blood and the inversion of the flow during the course of extracorporeal treatment lead to various drawbacks: a constructional complication, a delay in carrying out the treatment, an invasive intervention on the blood, quite removed from the course of normal treatment.

WO 02/04044 teaches a method for identifying problems in arterial flow during an extracorporeal blood treatment in which the blood is transferred, by means of a positive displacement pump, from the vascular access of a patient to a blood treatment device through an arterial line and then sent by the treatment device to the vascular access through a venous line of the extracorporeal circuit. The method consists in measuring the amplitude of the periodic variations in pressure in the venous line induced by the rotation of the blood pump, by comparing the variations with a threshold value and generating a control signal if the threshold value is exceeded. WO 02/04044: further describes another method according to which, during a dialysis treatment, the amplitude of the periodical variations of, the pressure of the dialysis fluid (and not the venous line) is measured. The result is compared with a threshold value and if the threshold value is exceeded a control signal is generated.

The methods described in WO 02/04044 are not however able to provide data relating to the blood flow rate at the vascular access.

U.S. Pat. No. 6,221,040 discloses a system for monitoring a vascular access during a dialysis treatment in which the pressures in both the arterial and venous branches of the extracorporeal blood system are monitored by pressure sensors. A computer unit generates first and second characteristic values for the integrity of the vascular access from measured arterial and venous pressures. An analyser unit analyses the integrity of the vascular access by comparing the first and second characteristic values to first and second ranges of predetermined values. Calculating a sum of the venous and arterial pressure generates the first characteristic value, and calculating a difference between the venous and the arterial pressure generates the second characteristic value.

The object of U.S. Pat. No. 6,221,040 is to provide a monitoring system that allows detection of the venous cannula slipping out of the vascular access as well as detection of a blood leak in the venous branch of the extracorporeal circuit. It is not directed to determination of fistula flow.

U.S. Pat. No. 5,866,015 and EP 0 773 035 disclose a method for determining hemodynamic parameters during an extracorporeal hemotherapy, including the steps of measuring the blood temperature in the arterial branch of the extracorporeal circuit, varying the blood flow in the extracorporeal circuit, storing the values of the extracorporeal blood flow and the measured values of the blood temperature, and determining a value of the blood flow from the stored sequence of value pairs of blood temperature and of extracorporeal blood flow, at which value, after it is exceeded, the amount of the change in the blood temperature within a specific blood flow interval is greater than a predetermined limiting value. The fistula flow is inferred from the determined blood flow value.

The method is based on the fact that the measuring curve existing in discrete measured values is able to be represented by two subfunctions, the first subfunction indicating the blood temperature as a function of the extracorporeal blood flow for blood flow values smaller than the fistula flow or equal to the fistula flow, and the second subfunction indicating the blood temperature as a function of the blood flow for blood flow values greater than or equal to the fistula flow. The intersection of the two subfunctions indicates the point where the extracorporeal blood flow equals fistula flow. Thus, from the “break point” of the characteristic function curve, i.e., from the discontinuity in the rise of the curve, the point is able to be defined where fistula recirculation begins, i.e., where blood flow equals fistula flow.

In addition to measuring temperature, the concentration of a blood constituent (hematocrit) can also be measured, as can the density, speed of sonic propagation, optical density, and conductivity or viscosity.

The blood characteristic to be measured must have a different value in the venous branch of the extracorporeal circuit than it does in the blood flowing to fistula. It is assumed that the blood characteristic, preferably the temperature, is kept constant in the venous branch of the extracorporeal circuit while the measured values are recorded. If this characteristic is not constant, a regulating device to keep the characteristic in the venous branch constant must be provided. In the case of a temperature measurement, for example, this can be realized as a temperature controller.

Another drawback of this method is that the delivery rate of blood pump, which predetermines the extracorporeal blood flow, is increased starting from a lower value to an upper limiting value which must be greater than the fistula flow to be expected. Fistula flows can only be determined within the adjustable blood flow range. Therefore the fistula flow is not determinable if it is equal to or greater than the upper limiting value of the adjustable blood flow range.

The prior art comprises the scientific publication entitled: “On-line dynamic measurement of fistula pressure during hemodialysis for detection of access stenosis and bad needle placement”, Abstract from the 24th EDTNA-ERCA Conference, Prague, 5–8 Jul. 1997, page 23, authors Polaschegg, Techert and Wizemann.

According to this publication it is possible to calculate the pressure of a vascular access by measuring the pressure in an extracorporeal blood circuit connected to the vascular access, with the aim of detecting any stenoses in the access itself.

In a scientific publication entitled “Dynamic pressure measurement for detection of blood access stenosis”, published in the EDTNA-ERCA Journal, 1998, XXIV, 4, on pages 39–44, authors Polaschegg, Techert and Wizemann, more detail is given on monitoring problems in a patient's vascular access. The method is based on the determination of the venous and arterial pressures (upstream of the blood pump) in an extracorporeal blood circuit connected to the vascular access to be monitored. The method comprises a preliminary stage in which, through in vitro tests in which the extracorporeal circuit is not connected to a real vascular access, fluid resistances in the arterial and venous lines of the extracorporeal circuit are calculated. During a second stage the extracorporeal circuit is connected to the real vascular access of the patient in order to initiate an extracorporeal treatment. During the extracorporeal treatment the venous and arterial pressures are calculated in the extracorporeal circuit. As the venous and arterial pressures in the extracorporeal circuit are known, as are the fluid resistances in the arterial and venous lines of the extracorporeal circuit, the pressures in the vascular access can be calculated. The dynamic measurement at different flow rates and the comparison with static measures enables stenoses at the vascular access to be identified.

The scientific publication entitled “Pressure drops in cannulas for hemodialysis”, author H. D. Polaschegg, published in The International Journal of Artificial Organs, Vol. 24, No. 9, 2001, pp. 614–623, relates to a method for determining a fall in pressure in an arterial or venous line in hemodialysis, with which the vascular access pressures can be determined starting from the pressures measured in the extracorporeal circuit of the hemodialysis machine.

The scientific publication entitled “Extracorporeal pressure monitoring and the detection of vascular access stenosis”, authors Kleinekofort, Kraemer, Rode and Wizemann, published in The International Journal of Artificial Organs, Vol. 25, No. 1, 2002, pp. 45–50, presents a method for identifying the presence of stenoses in a vascular access, even where the stenosis is located between the withdrawal needle and the return needle. The method comprises measuring the static pressures in the arterial and venous lines of an extracorporeal circuit and in calculating the pressures at the vascular access at the withdrawal point and the return point. These pressures, which correspond to the pressures which would be measured by two pressure sensors directly connected to the withdrawal and return needles, are used in order to identify the presence of a stenosis. A knowledge of the pressures both at the point of withdrawal and at the point of return of the vascular access provides more accurate indications and enables a first approximate localization of the stenosis, especially enabling to detect if the stenosis is in venous tract or is located between the needles.

The method described here is not however able to determine the blood flow rate in the vascular access.

The publication entitled “Utility of intra-access pressure monitoring in detecting and correcting venous outlet stenoses prior to thrombosis”, in Kidney International, Vol. 47 (1995), pages 1364–1373, authors Besarab, Sullivan, Ross, Moritz, teaches a method for deriving the pressure internally of the vascular access (intra-access pressure) from the pressure measured in the hemodialysis machine, as a function of the type of needle used, the blood flow rate of the hemodialysis machine, and the hematocrit of the blood. Other methods for determining the pressure at the vascular access are cited or described in the following publications:

-   -   “Detection of access strictures and outlet stenoses in vascular         accesses. Which test is best?”, in ASAIO Journal, 1997, Vol. 43:         pages M543–M547, authors Besarab, Lubkowski, Frinak, Ramanathan,         Escobar;     -   “Simplified measurement of intra-access pressure”, in Journal of         the American Society of Nephrology, 1998, Vol. 9, pages 284–289,         authors Besarab, Frinak, Sherman, Goldman, Dumpler, Devita,         Kapoian, Al-Saghir, Lubkowski;     -   “Effect of systemic hemodynamics on flow within vascular         accesses used for hemodialysis”, in ASAIO Journal 2001, Vol. 47,         pages 501–506, authors Besarab, Lubkowski, Vu, Aslam, Frinak;     -   “Dynamic venous access pressure ratio test for hemodialysis         access monitoring”, in American Journal of Kidney Disease, Vol.         40, N^(o) 4 (October), pages 760–768, 2002, authors Frinak,         Zasuwa, Dunfee, Besarab, Yee.

An abstract entitled “A novel model-based method for monitoring the hemodialysis vascular access”, published in the Journal of the American Society of Nephrology, 2001, Vol. 12, N. A1513, pages 294A–295A, authors Lodi, Monari, Fava, Paolini, Grandi, Galato, Cavalcanti, cites a mathematical model based on the hemodynamic description of the vascular access which enables the arterial and venous pressures at the vascular access to be calculated and also the flow in vascular access starting from extracorporeal arterial and venous pressures. The model, which includes three parameters (resistance to flow of the anastomosis, resistance between arterial and venous access, the resistance which expresses the efficiency of venous circulation drainage), was used to analyse the data gathered during a normal hemodialysis therapy operation. The abstract states that the extracorporeal venous and arterial pressures were measured after having set four different flow rates on the blood pump and that the above-cited parameters included in the mathematical model were calculated using the mathematical model.

SUMMARY OF THE INVENTION

The present invention provides a system for controlling vascular access adequacy during an extracorporeal blood treatment.

An aim of the invention is to enable calculation of some hemodynamic parameters at the vascular access. Knowledge of these parameters enables both regulation of the blood pump flow rate operation in the extracorporeal circuit and intervention in case of detection of a pathological situation in the vascular access.

A further aim of the invention is to enable evaluation of the blood flow circulating in the vascular access of a patient during an extracorporeal blood treatment.

A further aim of the invention is to make available a system for evaluating vascular hydraulic resistance in various tracts of the patient's vascular system. In particular, an aim of the invention is to evaluate vascular resistance upstream of the blood withdrawal zone from the vascular access, downstream of the blood return zone, and in the tract of vascular access comprised between the withdrawal zone and the return zone.

An advantage of the invention is that it provides indicative values of the efficiency of the vascular access simply, automatically, using devices (such as for example pressure transducers, blood pump, drainage pump) which are normally already present in machines for extracorporeal blood treatment. A further advantage is that the invention enables monitoring of the vascular access at any time during the extracorporeal blood treatment.

A further advantage of the invention is that the monitoring procedure does not cause extra stress to the patient. The procedure can be carried out by means of variations in the blood pump or the drainage pump flow rates, or both, within flow rate intervals which are normally compatible with the extracorporeal treatment the patient undergoes. The intervals can be those normally used during the course of therapy.

These aims and others besides are all attained by the invention as it is characterised in one or more of the appended claims.

In a special function of the invention, a mathematical model is used which contains at least two parameters in which a first parameter relates to the hemodynamics of the vascular access, and a second parameter relates to the blood flow rate in the extracorporeal circuit.

The mathematical model comprises a third parameter relating to at least one blood characteristic: this characteristic can be any physical, chemical or physical-chemical property thereof which characterises the blood in a vessel and which can be related to the blood flow rate in that vessel. A peculiarity of the invention is that the mathematical model used describes the relationship between the selected blood property (physical, chemical or physical-chemical) and the blood flow rate in the vessel. In particular the mathematical model describes the relationship in the vascular access. For example, the mathematical model can describe the fluid-dynamic situation of the vascular access; the model can describe a relationship between the difference of pressure at two points of the vascular access and the flow rate crossing the points. Apart from the pressure it is also possible to select other properties (physical, chemical or physical-chemical) of the blood which are influenced by the flow rate, such as, for example: the difference in induced potential, speed of sound, optical characteristics, temperature, concentration of an indicator, and so on.

According to the invention, the monitoring of the vascular access is performed by varying the flow rate of at least one fluid (for example blood or the product of ultrafiltration), which runs either in the extracorporeal circuit or in at least one hydraulic line (for example an ultrafiltration line) connected to the extracorporeal circuit.

The monitoring can be carried out by varying both the above-cited flows.

The monitoring determines the values of at least one characteristic of the blood, in at least one zone of the blood circulation path, and at at least two different values of the flow rate of the fluid.

As mentioned above, the cited characteristic of the blood can be a physical, chemical or chemical-physical one. In an embodiment of the invention, among the various characteristics of the blood that depend on blood flow, the selected characteristic to be used is the pressure.

The monitoring procedure involves calculating one or more of the hemodynamic parameters of the vascular access contained in the mathematical model, using the values of the blood characteristic determined previously during the course of the procedure.

In an embodiment of the invention, a multiplicity of values of the blood characteristic is determined; then the said hemodynamic parameters are calculated, by means of the mathematical model, using approximation algorithms (of known type). The algorithms can be chosen, for example, from those which enable determination of the value of the hemodynamic parameter, by virtue of which the blood characteristic values calculated using the mathematical model, at different flow rate values, are those which are closest to the blood characteristic values which were previously determined during the course of the procedure, at the same flow rate values.

In an embodiment of the invention, the mathematical model used is descriptive of the pressure variation at the vascular access: it comprises at least one hemodynamic parameter relative to at least one characteristic of the vascular access; at least one parameter relative to the blood characteristic; and at least one parameter relative to the blood flow rate in the extracorporeal circuit.

The hemodynamic parameter can be relative to at least one of the following characteristics of the vascular access: the blood flow rate upstream of a withdrawal zone of the blood from the access, the blood flow rate between the withdrawal zone and a blood return zone at the access, the blood flow rate downstream of the blood return zone, the vascular hydraulic resistance upstream of the blood withdrawal zone from the access, the vascular hydraulic resistance between the blood withdrawal zone and the blood return zone, and the vascular hydraulic resistance downstream of the blood return zone.

In a further embodiment of the invention, the monitoring procedure includes determining the values assumed by the blood characteristic in at least two zones of the blood circulation path (where the blood circulation path comprises both the intracorporeal circuit and the extracorporeal circuit) and at at least two different flow rate values of one fluid (blood or the product of ultrafiltration).

In a further embodiment of the invention, the monitoring procedure includes determining the values assumed by the blood characteristic in at least one zone of the blood circulation path and at at least two different flow rate values of two fluids (blood and the product of ultrafiltration).

In a further embodiment of the invention, the monitoring comprises a measuring stage of a blood characteristic, in a zone of the extracorporeal circuit arranged downstream of the blood withdrawal zone, or in a zone arranged upstream of the blood return zone, or in both above zones. The monitoring includes determining the blood characteristic in the vascular access, in the withdrawal zone, or in the return zone, or in both zones, by means of one or more mathematical models describing the variation of the said blood characteristic between the zones of withdrawal and return in the vascular access and the measuring zones in the extracorporeal circuit. The mathematical models can be, in particular, models descriptive of the variation of the said blood characteristic in the passage through the arterial or venous needles. In an embodiment of the invention, these mathematical models comprise at least one parameter which is relative to the blood flow, or at least one parameter relative to the hematocrit of the blood, or both said parameters. In particular the mathematical models can be represented by one or more interpolating formulas of experimental data; the formulas can be, for example, second-order polynomials with one or more parameters chosen between the flow rate and the hematocrit of the blood.

In a special operation of the invention, at regular time intervals the monitoring procedure determines the values assumed by the blood characteristic in at least one zone of the blood circulation path during the flow rate change, evaluates the variation of the blood characteristic, selects the values assumed by the blood characteristic when the variation has exceeded a threshold limit value, and uses the selected values to calculate the value of the blood characteristic at the vascular access.

In a further special operation of the invention, at regular time intervals the monitoring procedure determines the values of the blood characteristic in two different zones of the blood circulation path during flow rate change, compares the variation of the blood characteristic detected in a first zone of the blood circulation path and the variation of the characteristic detected in a second zone thereof, selects the values of the blood characteristic when the difference between the variations has exceeded a threshold limit value, and uses the selected values in calculating the value of the blood characteristic at the vascular access.

In another characteristic of the invention, in calculating the value of the characteristic of the vascular access, the monitoring procedure considers the values of the blood characteristic in a stationary blood flow situation, i.e. after having kept the flow rate constant for a determined period of time.

The monitoring procedure is applied by means of a machine for blood treatment in an extracorporeal circuit, in particular for a machine for treatment of kidney failure, predisposed to perform one or more of the following therapies: hemodialysis, hemofiltration, hemodiafiltration, pure ultrafiltration, plasmapheresis.

The machine is provided with a timer for carrying out the monitoring procedure at least once during the extracorporeal treatment.

The monitoring procedure can be initiated on command of an operator, or automatically at a predetermined moment during the treatment.

The extracorporeal circuit can be included in the complex of fluid distribution lines, of the disposable type, normally removably associated and used in a machine for treatment of renal failure.

The machine is normally equipped with pressure transducers operating in the blood withdrawal line, before the blood pump, and in the blood return line, after the blood treatment unit.

Further characteristics and advantages of the present invention will better emerge from the detailed description that follows, of a specific embodiment of the invention, illustrated purely in the form of a non-limiting example in the figures of the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The description will be made herein below with reference to the appended figures of the drawings, here given by way of non-limiting illustration, in which:

FIG. 1 is a diagram of a machine for an extracorporeal blood treatment provided with a monitoring device of the vascular access according to the invention;

FIG. 2 is a diagram of blood flow in a patient connected up to the machine of FIG. 1;

FIG. 3 is an electrical diagram which describes by analogy the circulation of extracorporeal and intracorporeal blood of the patient subjected to the extracorporeal treatment with the machine of FIG. 1;

FIG. 4 shows a diagram of the relation between ΔP_(f) and q_(b), where ΔP_(f)=P_(af)−P_(vf) (difference between arterial pressure in the vascular access P_(af) and venous pressure in the vascular access P_(vf)) and q_(b) is the extracorporeal flow rate of the blood;

FIG. 5 is a diagram of the relation between (P_(vf)−P_(v)) e q_(uf), where (P_(vf)−P_(v)) is the difference between the venous pressure in the vascular access P_(vf) and the systemic venous pressure P_(v), and q_(uf) is the ultrafiltration flow rate.

DETAILED DESCRIPTION

The machine illustrated in FIG. 1 is a machine for hemodiafiltration comprising a unit for an extracorporeal blood treatment (a filter for hemodiafiltration 1) having two chambers 2, 3 separated by a semipermeable membrane 4. A first chamber 2 has an inlet which is connected to an arterial line 5 (blood withdrawal line from the patient) of an extracorporeal blood circuit. The arterial line 5 is connectable with a vascular access 6 of a patient by means of an access tool constituted in the example by an arterial needle N_(A). The arterial line 5 is provided with a pressure sensor 8 and a positive displacement pump 9 for blood circulation along the extracorporeal circuit in the direction of the arrow 7.

The first chamber 2 has an outlet connected to a venous line 10 (blood return line to the patient) of the extracorporeal blood circuit. The venous line 10 is connectable to the vascular access 6 of the patient by means of an access tool constituted in the illustrated embodiment by a venous needle N_(V). The venous line 10 is provided with a pressure sensor 12.

The second chamber 3 of the filter 1 has an inlet connected to a supply line 14 of a fresh treatment fluid (dialysis liquid) and an outlet connected to a discharge line 15 of a discharge fluid (the dialysis liquid and the ultrafiltered liquid). The supply line 14 is provided with a supply pump 13 of the fresh treatment fluid. The discharge line 15 is provided with a drainage pump 16 for the circulation of the discharge fluid in the direction of the arrow 11.

The dialysis machine further comprises a control and calculation unit 17 connected to a screen and also to a keyboard through which the user communicates to the control and calculation unit the setting values for machine operation. One of the setting values which the control and calculation unit 17 receives from the user is the blood flow rate q_(b) in the arterial blood withdrawal line 5. The control and calculation unit 17 can control the speed of the blood pump 9 in order to have the predetermined value of flow rate q_(b). The control and calculation unit 17 can be connected to at least one measuring device, able to provide information relating to the effective blood flow rate in the arterial line. The measuring device can comprise, for example, a flowmeter, or an encoder connected to the rotor of a blood pump. The control and calculation unit 17 is further connected to the pressure sensors 8 and 12 and receives therefrom the signals indicating the detected pressure.

The control and calculation unit 17 controls the operation of the various motor devices of the machine, in particular the blood pump 9 and drainage pump 16, according to the instructions received from the user and the programmed algorithms contained in its memory.

The machine can further comprise sensors (of known type and not illustrated) for detecting the blood viscosity upstream and downstream of the treatment unit 1. The sensors can comprise, for example, measuring devices for the blood hematocrit level.

The control and calculation unit is programmed to carry out, automatically or by request of the user, a series of operations which enable the vascular access to be monitored.

FIG. 2 shows the patient's blood circulation subjected to extracorporeal treatment with the machine of FIG. 1. The vascular access 6, through which the extracorporeal blood circuit is connected to the cardio-vascular circuit of the patient is, in the embodiment, a fistula of the Cimino-Brescia type. In FIG. 2 H indicates the patient's heart, P denotes the pulmonary circuit, V denotes the vascular system (or systemic circuit, or intravascular circuit or intracorporeal circuit).

The arterial line 5 and the venous line 10 are connected at one end to the vascular access 6 and at the other end to the dialysis filter 1.

FIG. 3 shows an electrical diagram which, by analogy, describes the blood circulation of the patient subjected to the extracorporeal blood treatment.

The legend to FIG. 3 is as follows.

Quantities controlled by the control unit 17:

q_(b) blood pump flow rate [ml/min]

q_(uf) ultrafiltration flow rate [ml/min]

Known quantities (measurable directly or indirectly or determinable from indirect measurements using a mathematical model):

P_(am) extracorporeal arterial pressure [mmHg]

P_(vm) extracorporeal venous pressure [mmHg]

E_(art) hydrostatic pressure related to the height level difference between the pressure sensor 8 in the arterial line of the extracorporeal circuit and the arterial needle N_(A) [mmHg]

E_(ven) hydrostatic pressure related to the height level difference between the pressure sensor 12 in the venous line of the extracorporeal circuit and the venous needle N_(V) [mmHg]

R_(am) hydraulic resistance of the extracorporeal arterial line [mmHg·min/ml]

R_(vm) hydraulic resistance of the extracorporeal venous line [(mmHg·min/ml]

P_(af) vascular access arterial pressure [mmHg]

P_(vf) vascular access venous pressure [mmHg]

P_(a) mean systemic arterial pressure (MAP) [mmHg]

P_(v) venous pressure (venous return pressure) [mmHg]

Unknown quantities to be determined:

q_(a) blood flow rate at the vascular access, upstream of the arterial access [ml/min]

q_(f) blood flow rate of artero-venous anastomosis in the vascular access tract comprised between the arterial access and the venous access, (q_(f)=q_(a)−q_(b)) [ml/min]

q_(v) blood flow rate downstream of the venous access, (q_(v)=q_(a)−q_(uf)) [ml/min]

R_(d) hydraulic resistance upstream of the vascular access [mmHg·min/ml]

R_(f) hydraulic resistance between the arterial access and the venous access [mmHg·min/ml]

R_(v) hydraulic resistance downstream of the vascular access [mmHg·min/ml]

In the diagram of FIG. 3 the extracorporeal blood circuit is traced in bold line, while the intracorporeal circulation in the vascular access is drawn in thin line.

The nodes where the extracorporeal circuit meets with the vascular access are the zones where pressures P_(af) e P_(vf) are determined (either directly measured or calculated).

Various methods are known, based on mathematical models, for calculating pressures P_(af) e P_(vf) from known pressures P_(am) e P_(vm) in the extracorporeal circuit. Some of these methods are described in the scientific publications cited in the present description. Herein below details will be given of a method founded on a new mathematical model based on the electrical diagram represented in FIG. 3.

In the following a mathematical model is shown, also based on the electrical diagram of FIG. 3, representative of the hemodynamics of the vascular access of an extracorporeal blood circuit in which the blood is removed from the patient through an arterial needle, is made to circulate through the extracorporeal circuit and is returned through a venous needle.

The mathematical model describes the variation of pressure in the vascular access as a function of the blood flow rate.

The mathematical model is expressed in the following three equations which can be derived from the electrical diagram represented in FIG. 3.

$q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$ P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b)) P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf)) where, as mentioned herein above, the symbols have the following meanings:

q_(a)=blood flow rate at the vascular access 6 (fistula), upstream of the withdrawal point of the arterial needle N_(A)

q_(b)=blood flow rate in the arterial line 5 of the extracorporeal circuit

P_(a)=mean systemic arterial pressure measured at patient's arm

P_(af)=arterial pressure in the vascular access 6, i.e. the pressure in the vascular access (in the embodiment, with a Cimino-Brescia fistula, this is a tract of arterialized vein) at the point of withdrawal of the arterial needle N_(A)

R_(d)=resistance of the tract of arterialised vein comprised between the anastomosis and the point of withdrawal of the arterial needle N_(A)

P_(vf)=venous pressure in the vascular access 6, i.e. the pressure in the fistula at the return point of the venous needle N_(V)

R_(f)=vascular resistance of the tract of fistula comprised between the two needles N_(A) and N_(V) and representing the resistance between the two points at which P_(af) and P_(vf) are determined

P_(v)=venous pressure of the blood in the distal venous branch; the P_(v) value can be unknown during the extracorporeal treatment; in this case it can be placed at a constant physiological value (e.g. P_(v)=0)

R_(v)=vascular resistance in the venous branch of the blood return zone at the zone where venous pressure P_(v) is evaluated; where P_(v)=0, the resistance R_(v) represents total venous resistance, i.e. the vascular resistance met by the blood in returning from the venous needle N_(V) to the heart H, which constitutes an indicative value of the drainage efficiency of the venous circulation

q_(uf)=ultrafiltration flow rate (in case of hemodiafiltration, q_(uf) is the difference between the discharge fluid flow rate in the discharge line 15 and the fresh dialysis fluid flow rate in the supply line 14).

The pressures in the above-indicated mathematical model relate to atmospheric pressure. The arterial and venous pressures P_(af) and P_(vf) in the vascular access are measurable directly, for example using pressure sensors operating directly on the vascular access 6 in proximity or internally of the arterial and venous needles N_(A) e N_(V).

As previously mentioned, the pressures P_(af) and P_(vf) are also determinable indirectly using a mathematical model which includes, among its parameters, pressures P_(am) and P_(vm) (arterial and venous pressures) measured in the extracorporeal circuit by the pressure sensors 8 and 12. The prior art comprises various mathematical models usable for calculating pressures P_(af) and P_(vf) when pressures P_(am) and P_(vm) are known. Some of the above-cited prior art contains examples of so-usable mathematical models. There follows a further example of a mathematical model usable for determining the intravascular pressures of the blood starting from the easily-measurable values of the extracorporeal blood pressures.

Determination of P_(af) and P_(vf) with P_(am) and P_(vm) Known

The mathematical model used comprises the two equations which can be derived from the electrical diagram of FIG. 3: P _(af) =P _(am) +E _(art) +R _(am) ·q _(b) P _(vf) =P _(vm) +E _(ven) −R _(vm)·(q _(b) −q _(uf))

Resistances R_(am) and R_(vm) can be considered equal, with satisfactory approximation, to the hydraulic resistance of the arterial needle N_(A) and, respectively, the venous needle N_(V); it is therefore assumed for the sake of simplicity that the whole drop in pressure in the arterial and venous lines is concentrated at the respective needles.

To calculate the hydraulic resistance R of a needle, the following mathematical model is used: it makes use of an equation which connects the hydraulic resistance of the needle with the blood flow rate and the blood hematocrit. R=(A ₂ ·q _(b) ² +A ₁ ·q _(b) +B ₂ ·Hct ² +B ₁ ·Hct+B ₀)·R _(poiseuille) where

q_(b)=blood flow rate

Hct=blood hematocrit

$R_{Poiseuille} = \frac{8 \cdot L}{\pi \cdot r^{4}}$

L=length of needle

r=radius of internal section of the needle

R_(Poiseuille) is the theoretical hydraulic resistance calculated using the Hagen-Poiseuille law for a liquid with viscosity equal to one.

A₂, A₁, B₂, B₁ and B₀ are coefficients characteristic of each needle, the value being obtained by means of experimental preliminary laboratory testing, by measuring the fall of pressure through the needle with different blood and hematocrit flow rates. In experimental tests the flow rate was varied within a range from 0 to 500 ml/minute, while the hematocrit was varied within a range from 30 to 45%. The coefficients differ for a same needle according to blood flow direction, that is whether the needle is used as an arterial needle or as a venous needle. These preliminary in vitro tests serve to experimentally characterise the needles which will then be used for the extracorporeal blood treatment. The tests include simulation of the extracorporeal treatment (for example dialysis) using a machine for performing the treatment (for example a dialysis machine) with an extracorporeal circuit lacking the device for effecting the treatment (for example lacking a dialyzer filter), causing bovine blood to circulate, exiting from a container and returning thereto. The blood is kept at a constant temperature of 37° C. The blood hematocrit is measured. The machine and the circuit used in the tests can be the same as those illustrated in FIG. 1.

At intervals of about 1 minute the blood pump flow rate q_(b) is changed, starting from a zero flow rate q_(b0)=0 ml/minute and increasing it by 50 ml/minute up to a maximum flow rate of 500 ml/minute (q_(b1)=50 ml/min, q_(b2)=100 ml/min, . . . , q_(bi)=i·50 ml/min, . . . , q_(b10)=500 ml/min). In general, the flow rate q_(b) assumes N different values q_(bi) with i=0, 1, 2, . . . , N (N≧3).

At each interval pressures P_(ami) and P_(vmi) are measured using the pressure sensors placed along the extracorporeal circuit. From each pressure value measured, P_(ami) and P_(vmi), we subtract the hydrostatic pressure due to the different blood level in the container with respect to the point of measurement of the pressure on the machine. From pressures P_(ami) and P_(vmi) we can deduce the pressure falls of the corresponding needles ΔP_(ai) and ΔP_(vi), with i=0, 1, 2, . . . , N (N≧3).

The same operations are repeated, each time controlledly changing the value of the hematocrit in the bovine blood. The blood flow rate values q_(b) are the same each time, i.e. q_(b)=q_(bi), with i=0, 1, 2, . . . , N.

The hematocrit can be varied by dilution with physiological solution (in this case the hematocrit diminishes each time). For each series of operations the value of the hematocrit is measured. Purely by way of an example, the operations can be performed with the following hematocrit values: about 44%, about 42%, about 40%, about 38%, about 36%, about 34%, about 32%. In general the value of the hematocrit Hct assumes M different Hct_(j) values with j=1, 2, . . . , M (with M≧2).

Thus, for each needle we obtain a number N·M of values ΔP_(aij) and ΔP_(vij) with i=0, 1, 2, . . . , N (with N≧3) e j=1, 2, . . . , M (with M≧2).

A processor calculates the hydraulic resistances of the needle, normalised with respect to the Poiseuille resistance, for one of the hematocrit values (for example Hct=Hct₁) according to the equation:

$R_{ai1} = {\frac{\Delta\; P_{ai1}}{q_{bi}} \cdot \frac{1}{R_{Poiseuille}}}$ $R_{vi1} = {\frac{\Delta\; P_{vi1}}{q_{bi}} \cdot \frac{1}{R_{Poiseuille}}}$ in which

R_(ai1)=resistance of the arterial needle at flow rate q_(b)=q_(bi) and with hematocrit Hct=Hct₁

R_(vi1)=resistance of the venous needle at flow rate q_(b)=q_(bi) and with hematocrit Hct=Hct₁

ΔP_(ai1)=pressure drop on the arterial needle at flow rate q_(b)=q_(bi) and with hematocrit Hct=Hct₁.

ΔP_(vi1)=pressure drop on the venous needle at flow rate q_(b)=q_(bi) and with hematocrit Hct=Hct₁.

Hence we obtain two series of values R_(ai1) and R_(vi1) of resistances (one arterial and the other venous) corresponding to a determined hematocrit value (in the example Hct=Hct₁), with i=0, 1, 2, . . . , N, with N=number of times we determine ΔP_(ai1) and ΔP_(vi1) at different flow rates q_(bi).

Each of the two series of values (R_(a) and R_(v)) is interpolated by the processor using a second-order polynomial: R=A ₂ q _(b) ² +A ₁ q _(b) +b ₁ and we thus obtain, for each type of needle, a pair of coefficients A₂ and A₁ for each flow direction (i.e. we obtain a pair of coefficients which characterise the arterial needle and a pair of coefficients which characterise the venous needle). Coefficient b₁ depends on the blood hematocrit value.

Coefficients B₂, B₁ and B₀ are obtained as follows.

Let us for a moment consider only one blood flow direction through the needle: for example, the arterial needle.

The processor also calculates the resistances R_(a) of the arterial needle for the other hematocrit values Hct=Hct_(j) (j=2, . . . , M), at different blood flow rates q_(b)=q_(bi) (i=0, 1, 2, . . . , N), thus obtaining various series of values:

$R_{aij} = {\frac{\Delta\; P_{aij}}{q_{bi}} \cdot \frac{1}{R_{Poiseuille}}}$

These values of R_(a) are interpolated, for each hematocrit value Hat, according to the blood flow rate q_(b), using a second order polynomial: R _(ai2) =A ₂ q _(b) ² +A ₁ q _(b) +b ₂ for Hct=Hct ₂ R _(ai3) =A ₂ q _(b) ² +A ₁ q _(b) +b ₃ for Hct=Hct ₃ . . . R _(aiM) =A ₂ q _(b) ² +A ₁ q _(b) +b _(M) for Hct=Hct _(M) with i=0, 1, 2, . . . , N (with N≧3), in order to obtain a series of values b_(j) (j=1, 2, . . . , M)

In substance, exemplifying the above-mentioned process step by step, for j=1 the processor interpolates values R_(ai1) (for Hct=Hct₁) according to the equation R _(ai1) =A ₂ q _(b) ² +A ₁ q _(b) +b ₁ and thus determines b₁.

Then it interpolates values R_(ai2) for j=2 (for Hct=Hct₂) following the equation R _(ai2) =A ₂ q _(b) ² +A ₁ q _(b) +b ₂ and determines b₂, and so on up until j=M, thus obtaining M values of b_(j).

At this point the processor makes a further interpolation, using the values of b_(j) according to the equation b=B ₂ Hct ² +B ₁ Hct+B ₀ and thus determines coefficients B₂, B₁ and B₀.

The same series of interpolations is effected using the data relating to the venous needle.

Hereafter we report some examples of values of the coefficients A₂, A₁, B₂, B₁ and B₀ experimentally obtained.

With a needle having the following characteristics: gauge=15 (internal diameter=1.6 mm), length=28 mm, the following is obtained:

A₂ (arterial)=−0.00004, A₁ (arterial)=0.0351,

B₂ (arterial)=0.0192, B₁ (arterial)=−0.9398,

B₀ (arterial)=21.059, R_(poiseuille)=0.022

A₂ (venous)=−0.000026, A₁ (venous)=0.0266, B₂ (venous)=0.0403,

B₁ (venous)=−2.2937, B₀ (venous)=41.969, R_(poiseuille)=0.022

With a needle having the following characteristics: gauge=16 (internal diameter=1.4 mm), length=33 mm, the following is obtained:

A₂ (arterial)=−0.00004375, A₁ (arterial)=0.0309,

B₂ (arterial)=0.0081, B₁ (arterial)=−0.3226,

B₀ (arterial)=8.3882, R_(poiseuille)=0.0442

A₂ (venous)=−0.00002875, A₁ (venous)=0.0193,

B₂ (venous)=0.0037, B₁ (venous)=0.0487,

B₀ (venous)=1.4565, R_(Poiseuille)=0.0442.

The control and calculation unit 17 memory is preloaded with the coefficient values A₂, A₁, B₂, B₁ and B₀ of the most commonly used needles (the memory contains two series of coefficients for each needle, one for each blood flow direction, i.e. a series relating to a needle's use as an arterial needle and as a venous needle). The control and calculation unit 17 recognises the needle used in the extracorporeal treatment time by time and consequently in the calculation of P_(af) and P_(vf) uses the coefficients relating to the needle being used. Recognition of the needle can be automatic (for example by means of an identification system associated to the needle) or can be user-guided.

Thus a mathematical model is defined, usable by the control and calculation unit 17 for determining the pressures in the vascular access by measuring the pressure in the extracorporeal circuit.

Herein below some operative methods are defined by means of which a processor in the control and calculation unit 17 of the machine can monitor the vascular access during an extracorporeal treatment.

First Monitoring Procedure

In this first operative mode q_(b) is varied at q_(uf)=constant (=0), while P_(am) and P_(vm) are measured.

The operative mode is now described step by step.

-   -   a. Determine values P_(af1) and P_(vf1) of the arterial pressure         and, respectively, the venous pressure in the vascular access         (fistula) at a known blood pump flow rate q_(b1).     -   b. Save and store values q_(b1), P_(af1) and P_(vf1) in a         memory.     -   c. Change the blood pump flow rate to a known value q_(b2). At         the same time the ultrafiltration flow rate q_(uf) is kept         constant.     -   d. Keep the blood pump flow rate at q_(b2) for a determined         period of time (for example about ten seconds) to let the system         become stable.     -   e. Determine values P_(af2) and P_(vf2) of the arterial pressure         and, respectively, of the venous pressure in the vascular access         (fistula) at blood pump flow rate q_(b2).     -   f. Save and store values q_(b2), P_(af2) and P_(vf2).     -   g. Steps c–f can be repeated for a desired number of times so as         to save and store a series of values q_(bi), P_(afi), P_(vfi),         with i =1, 2, 3, . . . , N, where N is an integer number greater         than 1.     -   h. Calculate R_(f) and q_(a) using the values stored in the         memory and the mathematical model expressed by the equation         P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b))     -   i. Save and store the values calculated for R_(f) and q_(a).     -   j. Calculate R_(v) using at least a part of the stored values         and the mathematical model expressed by the equation         P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf))     -   k. Save and store the calculated value for R_(v).     -   l. Calculate R_(d) using at least a part of the stored values         and the mathematical model expressed in the equation

$q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$

-   -    where P_(a) (mean systemic arterial pressure or MAP) is         measured at the patient's arm in known ways and the measured         value of P_(a) is transmitted to the control and calculation         unit 17.     -   m. Save and store the value calculated for R_(d).

The calculation of R_(f) and q_(a) in point h can be done in the following way.

The stored values of q_(bi), P_(afi) and P_(vfi), with i=1, 2, . . . , N (with N≧2), are introduced into the equation P _(af) −P _(vf) =R _(f)·(q _(q) −q _(b)) so as to obtain a system of N equations with 2 unknowns q_(a) and R_(f). ΔP _(f1) =R _(f)·(q _(a) −q _(b1)) ΔP _(f2) =R _(f)·(q _(a) −q _(b2)) . . . ΔP _(fN) =R _(f)·(q _(a) −q _(bN)) where ΔP_(fi)=P_(afi)−P_(vfi) with i=1, 2, . . . , N (N≧2)

The unknown quantities q_(a) and R_(f) can be determined by calculating the optimal solution of the above-indicated equation system.

If N=2 the system has an analytical solution.

If N>2 the two unknowns q_(a) and R_(f) can be determined using an optimisation algorithm.

For example the processor calculates the two values, one q_(a) and the other R_(f), for which the corresponding values of ΔP_(f) calculated by the above-indicated system of equations are the closest to the ΔP_(fi) values previously determined at point e.

The following calculation procedure can be used. Using the values stored in memory, q_(bi), P_(afi) and P_(vfi), by means of a mathematical interpolation algorithm previously stored in memory the processor determines a linear equation which approximates the relation between ΔP_(f) and q_(b). Then the value of q_(b) at ΔP_(f)=0 is calculated, using the above-indicated linear equation. The value of q_(b) at ΔP_(f)=0 is assumed to be equal to the flow rate q_(a) of the vascular access. The value of q_(a) thus determined is stored in memory. Further, the processor calculates the value assumed by ΔP_(f) at q_(b)=0, once more using the same linear equation. The value of ΔP_(f) at q_(b)=0 is assumed to be equal to the product of R_(f)·q_(a). At this point, using the previously-stored value of q_(a) the value of R_(f) can be calculated with a simple quotient.

Graph ΔP_(f)−q_(b) of FIG. 2 illustrates this mode of procedure. The points in FIG. 2 represent the determined values ΔP_(fi) of ΔP_(f) according to the blood pump flow rate q_(b). The straight line interpolating the various points is the graphic representation of the linear mathematical relation which connects ΔP_(f) with q_(b).

The interpolation method can be any known linear interpolation method. The straight line of interpolation intersects the horizontal axis (q_(b)) at q_(a) and the vertical axis (ΔP_(f)) at R_(f)·q_(a).

Another way of calculating q_(a) and R_(f) is based on the description of the relation between q_(b) and ΔP_(f) using a non-linear mathematical relation (for example a polynomial of a degree greater than one), derived by the processor with an interpolation method using the values stored in the memory q_(bi), P_(afi) e P_(vfi). After having derived this non-linear relation, the value assumed by q_(b) at ΔP_(f)=0 is assumed to be equal to the flow rate q_(a) of the vascular access. The value of q_(a) thus determined is stored in memory. Further, the processor calculates the value assumed by ΔP_(f) at q_(b)=0, using the above-cited non-linear equation as well. The value of ΔP_(f) at q_(b)=0 is assumed to be equal to the product of R_(f)·q_(a). At this point, using the previously-stored value of q_(a) it is possible to calculate, by a simple division, the value of R_(f). This value represents, in the embodiment, the value of hydraulic resistance R_(f) at point q_(b)=0 (i.e. at zero blood flow rate in the extracorporeal circuit).

At point c., the blood pump flow rate is varied from q_(b1) to q_(b2) so that, in consequence of the change of flow rate q_(b2)−q_(b1), the pressure difference ΔP_(f)=P_(af)−P_(vf) varies significantly in absolute value and sufficiently to be appreciated (for example at least 2 mmHg), i.e. so that |ΔP _(f1) −ΔP _(f2)|≧2 mmHg, where ΔP _(f1) =P _(af1) −P _(vf1) and ΔP _(f2) =P _(af2) −P _(vf2)

The same occurs for each flow rate change from q_(bi) to q_(b(i+1)). The values of q_(bi) are selected so that the difference between the minimum value and the maximum value of q_(bi) does not exceed a predefined value (for example about 600 ml/min) in order that q_(a) and R_(f) can be considered as constant in the calculation with good approximation.

At point c. the ultrafiltration flow rate q_(uf) is kept constant=0.

At point j. the resistance R_(v) is calculated assuming q_(uf)=0. The R_(v) stored in memory can be one of the estimated R_(vi) or the mean value of the estimated R_(vi).

$R_{vi} = \frac{P_{vfi} - P_{v}}{q_{a}}$

At point l. the resistance R_(d) stored in the memory can be one of the R_(di) calculated with equation (1) or the mean value of the calculated R_(di).

$R_{di} = \frac{P_{a} - P_{afi}}{q_{a}}$ Second Monitoring Procedure

In the second operative mode q_(uf) is changed to q_(b)=constant (not zero), while P_(am) and P_(vm) are measured.

The operative mode is now described step by step.

-   -   a. Determine values P_(af1) and P_(vf1) of the arterial pressure         and, respectively, of the venous pressure in the vascular access         (fistula) at a known ultrafiltration flow rate q_(uf1) at a         predetermined blood pump flow rate q_(b).     -   b. Save and store values q_(uf1), P_(af1) and P_(vf1).     -   c. Change the ultrafiltration flow rate to a known value         q_(uf2). At the same time the blood pump flow rate q_(b) is kept         constant and equal to the initial flow rate of point a.     -   d. Keep the ultrafiltration pump flow rate at value q_(uf2) for         a determined period of time (for example about ten seconds) to         let the system become stable.     -   e. Determine values P_(af2) and P_(vf2) of the arterial pressure         and, respectively, the venous pressure in the vascular access         (fistula) at ultrafiltration flow rate q_(uf2) of the blood         pump.     -   f. Save and store values q_(uf2), P_(af2) and P_(vf2).     -   g. Steps c–f can be repeated for a desired number of times so as         to save and store a series of values q_(ufi), P_(afi), P_(vfi),         with i=1, 2, 3, . . . , N, where N is an integer number greater         than 1.     -   h. Calculate q_(a) and R_(v) using the values stored in the         memory and the mathematical model expressed in the equation         P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf))     -   i. Save and store the values calculated for R_(v) and q_(a).     -   j. Calculate R_(f) using at least a part of the stored values         and the mathematical model expressed in the equation         P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b))     -   k. Save and store the calculated value for R_(f).     -   l. Calculate R_(d) using at least a part of the stored values         and the mathematical model expressed in the equation

$q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$

-   -   m. Save and store the value calculated for R_(d).

At point c., the ultrafiltration flow rate is changed from q_(uf1) to q_(uf2) so that, in consequence of the change in flow rate q_(uf2)−q_(uf), the difference of pressure ΔP_(vf)=P_(vf)−P_(v) significantly varies in absolute terms sufficiently to be appreciated (for example at least 3 mmHg), i.e. so that |ΔP _(vf1) −ΔP _(vf2)|≧3 mmHg, where ΔP _(vf1) =P _(vf1) −P _(v) and ΔP _(vf2) =P _(vf2) −P _(v)

The same can be said for each flow rate change from q_(ufi) to q_(uf(i+1)).

At point c. the blood flow rate in the extracorporeal circuit q_(b) is kept constant at a known value which is not zero.

At point h. the calculation of R_(v) and q_(a) is performed in the following way.

The stored values of q_(ufi), P_(afi) and P_(vfi), with i=1, 2, . . . , N (with N≧2), are introduced in the equation P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf)) so as to obtain a system of N equations with 2 unknown quantities q_(a) and R_(v). P _(vf1) −P _(v) =R _(v)·(q _(a) −q _(uf1)) P _(vf2) −P _(v) =R _(v)·(q _(a) −q _(uf2)) . . . P _(vfN) −P _(v) =R _(v)·(q _(a) −q _(ufN))

The unknown quantities q_(a) and R_(v) can be determined by calculating the optimal solution of the above-indicated equation system.

If N=2 the system has an analytical solution.

If N>2 the two unknowns q_(a) and R_(v) can be determined using an optimization algorithm.

A calculation procedure which can be used is the following. Using the values stored in memory, q_(ufi) and P_(vfi), the processor determines, by means of a mathematical interpolation algorithm previously stored in memory, a linear equation which approximates the relation between ΔP_(vf) and q_(uf) where ΔP_(vf)=P_(vf)−P_(v). Then the value assumed by q_(uf) at P_(vf)−P_(v)=0 is calculated, using the above-indicated linear equation. The value of q_(uf) at ΔP_(vf)=0 is assumed to be equal to the flow rate q_(a) of the vascular access. The value of q_(a) thus determined is stored in memory. Further, the processor calculates the value assumed by ΔP_(vf) at q_(uf)=0, once more using the same linear equation. The value of ΔP_(vf) at q_(uf)=0 is assumed to be equal to the product of R_(v)·q_(a). At this point, using the previously-stored value of q_(a) the value of R_(v) can be calculated by a simple division.

The plot of ΔP_(vf) as a function of q_(uf) in FIG. 5 illustrates this mode of procedure. The points in FIG. 5 represent the determined values ΔP_(vfi)=P_(vfi)−P_(v) of ΔP_(vf) as functions of the ultrafiltration pump flow rate q_(uf). The straight line interpolating the various points is the graphic representation of the linear mathematical relation which connects ΔP_(f) with q_(uf). The interpolation method can be any known linear interpolation method. The straight interpolating line intersects the horizontal axis q_(uf) at q_(a) and the vertical axis of ΔP_(vf) at R_(v)·q_(a).

At point j. (determination of R_(f)) the following procedure is observed.

For each of the estimated values of P_(afi) and P_(vfi), a corresponding value of R_(fi) is calculated using the above-indicated equation, from which it is obtained:

$R_{fi} = \frac{P_{afi} - P_{vfi}}{q_{a} - q_{b1}}$

The R_(f) value stored at point k. can be one of the calculated values for R_(fi) or the mean value of the R_(fi) values.

At point l. (determination of R_(d)) the following procedure is observed.

For each of the estimated values of P_(afi), a corresponding value of R_(di) is calculated using the above-indicated equation:

$R_{di} = \frac{P_{a} - P_{afi}}{q_{a}}$

The R_(d) value stored at point l. can be one of the calculated values R_(di) or the mean value of the R_(di) values.

Third Monitoring Procedure

The equations which define the mathematical model of the vascular access used previously:

$q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$ P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b)) P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf)) can be reformulated so as to evidence the dependence of P_(af) and P_(vf) on P_(a), q_(b), q_(uf) and P_(v) through the unknown parameters R_(d), R_(f) and R_(v). The reformulated equations are as follow:

$P_{af} = {{\frac{R_{f} + R_{v}}{R_{d} + R_{f} + R_{v}} \cdot P_{a}} - {\frac{R_{d} \cdot R_{f}}{R_{d} + R_{f} + R_{v}} \cdot q_{b}} - \mspace{70mu}{\frac{R_{d} \cdot R_{v}}{R_{d} + R_{f} + R_{v}} \cdot q_{uf}} + {\frac{R_{d}}{R_{d} + R_{f} + R_{v}} \cdot P_{v}}}$ $P_{vf} = {{\frac{R_{v}}{R_{d} + R_{f} + R_{v}} \cdot P_{a}} + {\frac{R_{f} \cdot R_{v}}{R_{d} + R_{f} + R_{v}} \cdot q_{b}} - \mspace{65mu}{\frac{R_{v} \cdot \left( {R_{d} + R_{f}} \right)}{R_{d} + R_{f} + R_{v}} \cdot q_{uf}} + {\frac{R_{d} + R_{f}}{R_{d} + R_{f} + R_{v}} \cdot P_{v}}}$

These equations can be rewritten as reported herein below. P _(af) =c _(a0) ·P _(a) +c _(a1) ·q _(b) +c _(a2) ·q _(uf)+(1−c _(a0))·P _(v) P _(vf) =c _(v0) ·P _(a) +c _(v1) ·q _(b) +c _(v2) ·q _(uf)+(1−c _(v0))·P _(v) in which:

$\begin{matrix} {c_{a0} = \frac{R_{f} + R_{v}}{R_{d} + R_{f} + R_{v}}} & {c_{a1} = {- \frac{R_{d} \cdot R_{f}}{R_{d} + R_{f} + R_{v}}}} & {c_{a2} = {- \frac{R_{d} \cdot R_{v}}{R_{d} + R_{f} + R_{v}}}} \\ {c_{v0} = \frac{R_{v}}{R_{d} + R_{f} + R_{v}}} & {c_{v1} = \frac{R_{f} \cdot R_{v}}{R_{d} + R_{f} + R_{v}}} & {c_{v2} = \frac{R_{v} \cdot \left( {R_{d} + R_{f}} \right)}{R_{d} + R_{f} + R_{v}}} \end{matrix}$

The third operating mode (as the following fourth and fifth operating modes) calculates at least a part of the coefficients c_(a0), c_(a1), c_(a2) and c_(v0), c_(v1), c_(v2) and from these derives R_(d), R_(f) and R_(v). The calculation of the coefficients is done starting from one or more known values for each of the following quantities: P_(a), q_(b), q_(uf), P_(v), P_(af) and P_(vf). The quantities P_(a), q_(b), q_(uf), P_(v) are known through measurement. The quantities P_(af) and P_(vf) are known by direct measurement of the pressures in the vascular access, or by a process of calculation starting from the measurement of the pressures in the machine P_(am) and P_(vm).

As the number of coefficients c_(a0), C_(a1), c_(a2), c_(v0), c_(v1), c_(v2) is greater than the number of the resistances R_(d), R_(f) and R_(v), there exists a multiplicity of relations between the coefficients and the resistances. In general, knowledge of three coefficients enables a determination of the resistances.

In the third operating mode both flow rates q_(b) and q_(uf) are varied and the arterial pressure in the machine P_(am) is measured, from which arterial pressure in the vascular access P_(af) is calculated.

In a specific embodiment in a first stage the pressure P_(am) at flow rates q_(b)=0 and q_(uf)=0 is measured; in a second stage pressure P_(am) at flow rates q_(b)≠0 and q_(uf)=0 is measured; in a third stage pressure P_(am) at flow rates q_(b)≠0 and q_(uf)≠0 is measured.

More in general, q_(b) at q_(uf)=constant (for example=0) is varied and P_(am) is measured at different values of q_(b). Thereafter q_(uf) at q_(b)=constant (for example≠0) is varied and P_(am) measured at different values of q_(uf).

In this third operating mode a mathematical model of the vascular access is used which is represented by one equation only: P _(af) =C _(a0) ·P _(a) +c _(a1) ·q _(b) +c _(a2) ·q _(uf)+(1−c _(a0))·P _(v) from which coefficients c_(a0), c_(a1), c_(a2) can be derived, which are sufficient by themselves for the calculation of the three resistances R_(d), R_(f), R_(v).

In this third operating mode at least one measurement is taken of the patient's arterial pressure P_(a). Further, distal venous pressure P_(v) is assumed to be zero; for this reason the equation used is simplified as follows: P _(af) =c _(a0) ·P _(a) +c _(a1) ·q _(b) +c _(a2) ·q _(uf)

The third operating mode is now described step by step.

-   -   a. Determine values P_(af0) of the arterial pressure in the         vascular access (fistula) and the systemic arterial pressure of         the patient P_(a0) at a known ultrafiltration flow rate         q_(uf1)=0 at a predetermined blood pump flow rate q_(b)=0.     -   b. Save and store values P_(a0) and P_(af0).     -   c. Calculate c_(a0) by means of the equation

$c_{a0} = \frac{P_{af0}}{P_{a0}}$

-   -   d. Save and store value c_(a0).     -   e. Change the blood flow rate q_(b) to a known value q_(b1). At         the same time the ultrafiltration flow rate q_(uf) is kept         constant and equal to the flow rate at point a. (=0).     -   f. Determine values P_(af1) and P_(a1) of the arterial pressure         in the vascular access (fistula) and, respectively, of the         patient at blood pump flow rate q_(b1).     -   g. Save and store values q_(b1), P_(af1) and P_(a1).     -   h. Steps d–f can be repeated for a desired number of times so as         to save and store a series of values q_(bi), P_(afi), P_(ai),         with i=1, 2, 3, . . . , N, where N is an integer number greater         than or equal to 1.

i. Determine c_(a1) by solving the system of equations: P _(afi) −c _(a0·P) _(ai) =c _(a1) ·q _(bi) with i=1, . . . , N (N≧1)

If N=1 it is sufficient to solve a linear equation with only an unknown quantity.

If N>1 the value of c_(a1) is found by means of an optimisation algorithm which determines the optimal solution for the above-cited system. The searched-for value can be the value of c_(a1) which minimises the error between the values of P_(af) calculated with the above system of equations, P_(afi)*, where the asterisk * indicates that the value has been calculated, and the P_(afi) values determined by measuring a pressure correlated with P_(af). The optimisation algorithm can be, for example, a linear regression algorithm.

-   -   j. Save and store value c_(a1).     -   k. Change the ultrafiltration flow rate to a known value q_(uf1)         not zero. At the same time the blood flow rate q_(b) has a known         value q_(bk) different to zero.     -   l. Determine values P_(af1) and P_(a1) of the arterial pressure         in the vascular access (fistula) and, respectively, of the         patient at ultrafiltration flow rate q_(uf1).     -   m. Save and store values q_(bk), q_(uf1), P_(af1) and P_(a1).     -   n. Steps k–m can be repeated for a desired number of times in         order to store a series of values q_(ufj), P_(afj), P_(aj), with         j=1, 2, . . . , M, where M is an integer number equal to or         greater than 1.     -   o. Determine c_(a2) by solving the following system of equations         P _(afj) −c _(a0) ·P _(aj) −c _(a1) ·q _(bk) =c _(a2) ·q _(ufj)         with j=1, 2, . . . , M (M≧1)

If M=1 it is sufficient to solve a linear equation with only an unknown quantity.

If M>1 the value of c_(a2) is found by means of an algorithm of optimisation which determines the optimal solution for the above system. The sought-after value can be the value of c_(a2) which minimises the error between the values of P_(af) calculated using the system of equations P_(afj)*, where the asterisk * indicates that the value is a calculated one, and the values of P_(afj) determined through measuring a pressure correlated by P_(af). The optimisation algorithm can be, for example, a linear regression algorithm (as at point i. above).

-   -   p. Save and store the determined value of c_(a2).     -   q. Determine R_(f), R_(v) and R_(d) by solving the following         system of equations which express the relation between c_(a0),         c_(a1), c_(a2) and R_(d), R_(f), R_(v).

$\begin{matrix} {R_{f} = {{- c_{a1}} \cdot \left( {1 + \frac{1}{{1/c_{a0}} - 1}} \right)}} \\ {R_{v} = {{- c_{a2}} \cdot \left( {1 + \frac{1}{{1/c_{a0}} - 1}} \right)}} \\ {R_{d} = {\left( {{1/c_{a0}} - 1} \right) \cdot \left( {R_{f} + R_{v}} \right)}} \end{matrix}$

The value of the resistance R_(f) can already be determined at step j. as both c_(a0) and c_(a1) are already known.

-   -   r. Save and store the first determined values of R_(f), R_(v)         and R_(d).     -   s. Determine q_(a) using one of the equations of the         mathematical model of the vascular access, for example:

$q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$

-   -   t. Save and store the value calculated for q_(a).

In steps from l. to n. the operation of measuring P_(aj) can be omitted; in this case the values stored and used for the calculation are the same P_(ai) values calculated at point h. at q_(b)=q_(b1) and q_(uf)=0, or at point a. at q_(b)=0 and q_(uf)=0.

Fourth Monitoring Procedure

Varying q_(b) at q_(uf)=constant (for example zero) and measuring P_(am) and P_(vm).

In this case too we calculate at least a part of the coefficients c_(a0), c_(a1), c_(a2) and c_(v0), c_(v1), c_(v2) from which R_(d), R_(f) and R_(v) are obtained. The calculation of the coefficients is done starting from the knowledge of one or more values for each of the following quantities: P_(a), q_(b), q_(uf), P_(v), P_(af) and P_(vf). The quantities P_(a), q_(b), q_(uf), P_(v) are known by measurements. The quantities P_(af) and P_(vf) are known by direct measurement of the pressures in the vascular access, or by means of a calculation process which uses the measured values of pressures P_(am) and P_(vm) in the extracorporeal circuit.

In the fourth operating mode the measures were taken at q_(uf)=0 and we use a mathematical model which includes both equations of P_(af) and P_(vf) which in this case are simplified into the following formulation: P _(af) =c _(a0) ·P _(a) +c _(a1) ·q _(b)+(1−c _(a0))·P _(v) P _(vf) =c _(v0) ·P _(a) +c _(v1) ·q _(b)+(1−c _(v0))·P _(v) In the fourth operating mode the processor determines the four coefficients c_(a0), c_(a1), c_(v0), and c_(v1) and from these it calculates the three resistances R_(d), R_(v), R_(f).

In the fourth operating mode the pressures P_(af) and P_(vf) in the vascular access are determined, either by direct measuring or by measuring pressures P_(am) e P_(vm) in the extracorporeal circuit and calculating P_(af) and P_(vf) by means of a mathematical model. The pressures P_(af) and P_(vf) are determined at different values of the blood flow rate q_(b). In the fourth operating mode, the arterial and venous pressures P_(a) and P_(v) of the patient are also considered in the calculation of the coefficients.

As coefficients c_(a0), C_(a1), c_(v0), and c_(v1) are greater in number than resistances R_(d), R_(f) and R_(v), there exists a multiplicity of relations between the coefficients and resistances. In general the knowledge of three coefficients enables determination of the resistances. It has been found that the most precise determination of the resistances R_(d), R_(f) and R_(v) is obtained by using the three coefficients, c_(a0), c_(a1), and c_(v0).

The fourth operating mode is now described step by step.

-   -   a. Determine pressures P_(af), P_(vf), P_(a), and P_(v) with the         blood pump flow rate and the ultrafiltration flow rate at nil         (q_(b)=0 and q_(uf)=0).     -   b. The values thus determined, P_(af0), P_(vf0), P_(a0) and         P_(v0), are stored in memory.     -   c. The processor calculates C_(a0) and c_(v0) by means of the         equations:

$\begin{matrix} {c_{a0} = \frac{P_{af0} - P_{v0}}{P_{a0} - P_{v0}}} \\ {c_{v0} = \frac{P_{vf0} - P_{v0}}{P_{a0} - P_{v0}}} \end{matrix}$

-   -   d. Change the blood flow rate to a known value q_(b)=q_(b1)≠0.     -   e. Determine at least one value of P_(af), P_(vf), P_(a) and         P_(v) when q_(b)=q_(b1).     -   f. Save and store values P_(af1), P_(vf1), P_(a1) and P_(v1)         above-determined.     -   g. Repeat steps from d. to f. for a predetermined number of         times N in order to obtain a series of values q_(bi), P_(afi),         P_(vfi), P_(ai) and P_(vi) with i=1, 2, . . . , N (N≧1)     -   h. Calculate c_(a1) as a solution for the system of equations         P _(afi) −c _(a0) ·P _(ai)−(1−c _(a0))·P _(vi) =c _(a1) ·q _(bi)

If N=1 the solution is immediate. If N>1 the solution is obtainable with an optimization algorithm, such as for example a linear regression algorithm.

-   -   i. Save and store the value of c_(a1).     -   j. Determine resistances R_(d), R_(f), and R_(v) by solving the         following equations which express the relation between c_(a0),         c_(a1), c_(v0) and R_(d), R_(f), R_(v):

$\begin{matrix} {R_{d} = \frac{c_{a1}}{c_{v0} - c_{a0}}} \\ {R_{f} = \frac{c_{a1}}{c_{a0} - 1}} \\ {R_{v} = \frac{c_{a1} \cdot c_{v0}}{\left( {c_{a0} - c_{v0}} \right) \cdot \left( {c_{a0} - 1} \right)}} \end{matrix}$

-   -   k. Save and store values R_(d), R_(f), and R_(v)         above-determined.     -   l. Determine the flow rate of the vascular access q_(a) using         one of the equations of the mathematical model, for example the         second:         P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b))

At point e., determination of the value of P_(v) can be performed in two ways.

The first consists in considering P_(v) constant (P_(v)=P_(v0)) during variation in the blood flow rate q_(b), thus ignoring the variations in the venous pressure P_(v) which actually occur during the various operative stages. Consequently the system of equations of point h. can be rewritten in the following way: P _(afi) −c _(a0) ·P _(ai)−(1−c _(a0))·P _(v0) =c _(a1) ·q _(bi)

The second way consists in considering the variations in P_(v) to be proportional to the variations in the arterial pressure P_(a), thus:

$P_{vi} = {P_{v0} \cdot \frac{P_{ai}}{P_{a0}}}$

This is equivalent to assuming resistances R_(d), R_(f) and R_(v) to be constant during variation of q_(b).

In this case the equation of point h. is:

${P_{afi} - {c_{a0} \cdot P_{ai}} - {\left( {1 - c_{a0}} \right) \cdot P_{v0} \cdot \frac{P_{ai}}{P_{a0}}}} = {c_{a1} \cdot q_{bi}}$

Note that by substituting, in the above equation, c_(a0) with the expression

$c_{a0} = \frac{P_{af0} - P_{v0}}{P_{a0} - P_{v0}}$ as in point c. of the present operating mode, the following equation is obtained:

${P_{afi} - {\frac{P_{af0}}{P_{a0}} \cdot P_{ai}}} = {c_{a1} \cdot q_{bi}}$ which is the same equation that appears at point i. of the third operating mode, in which the contribution of P_(v) was ignored. Fifth Monitoring Procedure

The fifth operating mode is similar to the third, with the difference that, instead of determining P_(af), P_(vf) is determined.

Briefly, the fifth operating mode consists in varying the blood flow rate q_(b) while maintaining the ultrafiltration rate q_(uf) constant, in varying the ultrafiltration rate while keeping the blood flow rate q_(b) constant, and in determining the venous pressure in the vascular access P_(vf) at various values of the above-mentioned flow rates. The processor determines the resistances R_(d), R_(f) and R_(v) and the flow rate q_(a) in the vascular access by calculating the coefficients c_(v0), c_(v1), c_(v2) using the equation P _(vf) =c _(v0) ·P _(a) +c _(v1) ·q _(b) +c _(v2) ·q _(uf)+(1−c _(v0))·P _(v) and the operative stages cited for the third operative mode.

The resistances are calculated by solving the following system of equations:

$c_{v0} = \frac{R_{v}}{R_{d} + R_{f} + R_{v}}$ $c_{v1} = \frac{R_{f} \cdot R_{v}}{R_{d} + R_{f} + R_{v}}$ $c_{v2} = {- \frac{R_{v} \cdot \left( {R_{d} + R_{f}} \right)}{R_{d} + R_{f} + R_{v}}}$

The flow rate of the vascular access q_(a) is calculated as in the third operative mode.

Note that, by means of the second monitoring procedure, q_(a) and R_(v) can be derived by determining two or more values for the venous pressure alone (P_(vm) in the machine or P_(vf) in the fistula), with the equation P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf)) while for the calculation of the values of R_(f) and R_(d), the values of arterial pressure (P_(am) or P_(af)) are also used, as well as the other two equations of the mathematical model:

$q_{a} = {{{\frac{P_{a} - P_{af}}{R_{d}}\mspace{14mu}{and}\mspace{14mu} P_{af}} - P_{vf}} = {R_{f} \cdot {\left( {q_{a} - q_{b}} \right).}}}$

Similarly a further monitoring procedure can be formulated on the basis of which the values of q_(a) and R_(d) are calculated, determining two or more values of only the arterial pressure (P_(am) in the machine or P_(af) in the fistula), using the equation

$q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$ while for calculating the values of R_(f) and R_(v) the values of the venous pressure (P_(vm) or P_(vf)) are also used, as well as the other two equations of the mathematical model: P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf)) and P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b)).

In all of the above-described modes, the measurements are taken with the system in a steady state. For example, the various measurements are taken after a certain time interval (for example about ten seconds) after the blood flow rate or the ultrafiltration rate has been changed.

Two numerical examples of the application of the invention are now reported.

FIRST EXAMPLE

This example uses the above-described first monitoring procedure, applied to the apparatus of FIG. 1.

Direct measurement of pressures P_(a), P_(af), P_(vf) were taken at different flow rate values q_(b). The measurements taken are reported in the following table.

q_(b) P_(a) P_(af) P_(vf) ΔP_(f) (ml/min) (mmHg) (mmHg) (mmHg) (mmHg) 300 100 51 42 9 200 52 41 11 100 54 40 14 400 51 42 9 500 50 43 7

The equation of the straight line interpolating points ΔP_(f) is as follows (see FIG. 4, where ΔP_(f) is a function of q_(b)) ΔP _(f)=0.016·(925−q _(b))

From which the following values are calculated

R_(f)=0.016 mmHg min/ml

q_(a)=925 ml/min

From the third equation of the mathematical model used (assuming P_(v)=0) we have q_(b1)=300 ml/min:

$R_{v} = {\frac{P_{vf1}}{q_{a}} = {0.045\mspace{20mu}{mm}\;{{Hg} \cdot \min}\text{/}{ml}}}$

Given P_(a)=100 mmHg, for q_(b1)=300 ml/min we obtain:

$R_{d} = {\frac{P_{a} - P_{af1}}{q_{a}} = {0.053\mspace{20mu}{mm}\;{{Hg} \cdot \min}\text{/}{ml}}}$

SECOND EXAMPLE

The second example uses the fourth monitoring procedure.

In the following the values of the pressure measured at different blood pump flow rates are reported.

q_(b) P_(a) P_(af) P_(vf) P_(v) (ml/min) (mmHg) (mmHg) (mmHg) (mmHg)  0 120 62 35 0 150 118 59 37 250 117 57 37 350 114 53 38

From these values we obtain:

$c_{a0} = {\frac{P_{af0} - P_{v0}}{P_{a0} - P_{v0}} = 0.52}$ $c_{v0} = {\frac{P_{vf0} - P_{v0}}{P_{a0} - P_{v0}} = 0.29}$

By applying a linear regression algorithm to the following equation: P _(afi) −c _(a0) ·P _(ai)−(1−c _(a0))·P _(v0) =c _(a1) ·q _(bi)

the following value for coefficient c_(a1) was found:

c_(a1)=−0.0155

After which the following resistance values were found:

R_(d)=0.069 mmHg min/ml

R_(f)=0.032 mmHg min/ml

R_(f)=0.042 mmHg-min/ml

From this we calculated:

$q_{a} = {\frac{P_{af0} - P_{vf0}}{R_{f}} = {842\mspace{14mu}{ml}\text{/}\min}}$ 

1. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; at least a second pump predisposed for circulation of a fluid in another of either the extracorporeal blood circuit or the fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood; and at least a third parameter relating to a flow rate (q_(b), q_(u)) of the fluid moved by the first pump; at least a fourth parameter relative to the flow rate (q_(b), q_(uf)) of the fluid made to circulate in the second pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access.
 2. The apparatus of claim 1, wherein the control and calculation unit is connected to the second pump, and wherein the monitoring procedure further comprises the following stages: varying the flow rate of the second pump; receiving signals corresponding to the values assumed by the blood characteristic at at least one zone of the blood circulation path and for at least two different values of the flow rate of the second pump; storing in the memory said values of the blood characteristic and the corresponding values of the second pump; and processing said stored values using the mathematical model for determining at least one value of the vascular access characteristic.
 3. The apparatus of claim 2, in which the control and calculation unit is programmed to maintain the flow rate of the first pump constant during the variation in flow rate of the second pump.
 4. The apparatus of claim 1, wherein the control and calculation unit is programmed for: receiving signals corresponding to the values assumed by the blood characteristic at at least two different zones of the blood circulation path and for at least two different values of the flow rate of the second pump; storing in the memory said values of the blood characteristic and the corresponding flow rate values of the second pump; and processing said stored values using the mathematical model for determining at least one value of the vascular access characteristic.
 5. The apparatus of claim 1, wherein the control and calculation unit is programmed to receive at least two signals, for at least two different values of the flow rate of the first pump and a same value of the flow rate of the second pump.
 6. The apparatus of claim 1, wherein the control and calculation unit is programmed to receive at least two signals, for at least two different values of the flow rate of the second pump and a same value of the flow rate of the first pump.
 7. The apparatus of claim 1, wherein the control and calculation unit is programmed to maintain the flow rate of the second pump constant during the variation in flow rate of the first pump.
 8. The apparatus of claim 1, wherein the control and calculation unit is programmed to perform a monitoring procedure comprising the following operative stages: changing the flow rate of the first pump; changing the flow rate of the second pump; receiving signals relating to the values of the blood characteristic in at least one zone of the blood circulation path, for at least two different values of the first pump flow rate and for at least two different values of the second pump flow rate; storing said values of the blood characteristic and corresponding values of the first pump flow rate and the second pump flow rate; and processing said values stored by means of the mathematical model to determine at least one value of the vascular access characteristic.
 9. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood; at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; and at least one parameter relating to at least one characteristic (P_(a), P_(v),) of a systemic circulation of a patient, wherein the characteristic of the systemic circulation of the patient is the systemic arterial pressure (P_(a)); a control and calculation unit connected to the memory and to the first pump, the control and calculation unit being configured to receive at least one signal corresponding to the at least one characteristic (P_(a), P_(v)) and being programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access.
 10. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, wherein the extracorporeal blood circuit is connected to the vascular access in a blood withdrawal zone and in a blood return zone, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood; and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access; said control and calculation unit being further connected to at least one pressure sensor configured to detect at least one value of the blood characteristic in a value detection zone that is between the blood withdrawal zone and a blood pump, said value detection zone also including the blood withdrawal zone, and said control and calculation unit being further configured to emit a signal corresponding to the value detected.
 11. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, wherein the extracorporeal blood circuit is connected to the vascular access in a blood withdrawal zone and in a blood return zone, comprising; at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood; and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access; said control and calculation unit being further connected to at least a first sensor and a second sensor, the second sensor being a pressure sensor, said first sensor being configured to detect at least one value of the blood characteristic in a first value detection zone that is comprised between the blood withdrawal zone and a blood pump, said first value detection zone also including the blood withdrawal zone, said second sensor being configured to detect at least one value of the blood characteristic in a second value detection zone between the blood pump and the blood return zone, the blood return zone being included in the second value detection zone; said first sensor being configured to emit a first signal corresponding to a value detected by the first sensor, and said second sensor being configured to emit a second signal giving a value detected by the second sensor.
 12. An apparatus for monitoring a vascular access associated to an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood, said characteristic (P) relating to blood pressure; and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm),) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access.
 13. The apparatus of claim 12, wherein the second parameter is a parameter relating to the blood pressure in a blood withdrawal zone of the vascular access.
 14. The apparatus of claim 12, wherein the second parameter is a parameter relating to the blood pressure in a blood return zone of the vascular access.
 15. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access, said mathematical model describing a pressure variation in the vascular access as a function of a blood flow rate, the mathematical model comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood; and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump: storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access.
 16. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access, wherein the mathematical model comprises one or more of the following equations: $q_{a} = \frac{P_{a} - P_{af}}{R_{d}}$ P _(af) −P _(vf) =R _(f)·(q _(a) −q _(b)) P _(vf) −P _(v) =R _(v)·(q _(a) −q _(uf)). said memory comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood; and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(f)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access.
 17. An apparatus for monitoring a vascular access associated to an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a first mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; and processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access; said control and calculation unit being configured to receive signals corresponding to the values of the blood characteristic in at least a first detection zone of the circuit, distant from a blood withdrawal zone from the vascular access and a second detection zone of the circuit, distant from a blood return zone of the vascular access; wherein said memory contains a second mathematical model of the variation of the blood characteristic between the blood withdrawal zone and the first detection zone and a third mathematical model for the variation of the blood characteristic between the blood return zone and the second detection zone; the control and calculation unit being programmed to process, using the second and third mathematical models, the values of the blood characteristic relating to the first and second detection zones, and to determine at least one value of the blood characteristic which relates to each of the blood withdrawal and return zones.
 18. The apparatus of claim 17, wherein at least one of the second and third mathematical models comprises at least one parameter relating to the blood flow rate.
 19. The apparatus of claim 17, wherein at least one of the second and third mathematical models comprises at least one parameter relating to hematocrit of the blood.
 20. The apparatus of claim 17, wherein: at least one of the second and third mathematical models comprises at least one series of experimentally-determined coefficients that are characteristic of an access tool (N_(A), N_(V)) used for connecting the extracorporeal circuit with the vascular access during a blood withdrawal or return stage; and the memory contains coefficients that are characteristic of a plurality of access tools (N_(A), N_(V)) of different types and is configured to recognize a type of access tool used time-by-time and to use, in at least one of the second and third mathematical models, the coefficients which are characteristic of a type of access tool recognized.
 21. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood, said characteristic relating to blood pressure; and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af, P) _(am), P_(vf), P_(vm)) assumed by the blood pressure in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf), of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; processing the values stored in memory by means of the mathematical model, in order to determine at least one value of a characteristic of the vascular access; receiving, at regular intervals, signals relating to the values of the blood characteristic in at least one zone of the blood circulation path during a variation of flow rate of the first pump; evaluating changes in the values of the blood characteristic; and using the blood characteristic values for a following processing operation when the variation has exceeded a threshold value, said threshold value being about 2 mm Hg.
 22. An apparatus for monitoring a vascular access associated with an extracorporeal blood circuit, comprising: at least a first pump predisposed for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit; a memory, containing a mathematical model of the vascular access comprising: at least a first parameter relating to at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(v)) at least a second parameter relating to at least one characteristic (P) of the blood and at least a third parameter relating to a flow rate (q_(b), q_(uf)) of the fluid moved by the first pump; a control and calculation unit connected to the memory and to the first pump and programmed to perform a monitoring procedure which comprises the following operating stages: varying the flow rate of the first pump; receiving the signals corresponding to the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by the characteristic (P) of the blood in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the first pump; storing in memory the values of the characteristic of the blood and the corresponding values of the flow rate of the first pump; processing the values stored in memory by means of the mathematical model, in order to determine at least one value of the characteristic of a vascular access; said control and calculation unit being further programmed to: reach a steady state after having maintained the flow rate of each pump at a constant rate for a determined period of time; store and process values of the blood characteristic in the steady state.
 23. A machine for treatment of blood in an extracorporeal circuit, comprising a monitoring apparatus according to any one of claims 1, 9, 10, 11, 12–15, 16, 17–20, and 21–8.
 24. A method for operating a blood treatment machine for determining hemodynamic parameters during extracorporeal blood treatment, wherein blood is sent to a blood treatment unit via an arterial line of an extracorporeal blood circuit which is connected with a vascular access, and is returned via a venous line of the extracorporeal blood circuit; at least a pump being configured for circulation of a fluid in at least one of the extracorporeal blood circuit and at least one fluid transport line cooperating with the extracorporeal blood circuit, the method comprising the stages of: varying the flow rate of the pump; determining the values (P_(af), P_(am), P_(vf), P_(vm)) assumed by a characteristic (P) of the blood wherein the said blood characteristic (P) is the blood pressure, in at least one zone of the blood circulation path and with at least two different values of the flow rate (q_(b), q_(uf)) of the pump; storing in a memory said values of the characteristic (P) of the blood and corresponding values of the flow rate of the pump; processing the values stored in the memory by calculating at least one solution of a mathematical model, in order to determine at least one value of at least one characteristic (R_(d), R_(f), R_(v), q_(a), q_(f), q_(a)) of the vascular access, the mathematical model describing a relationship between the difference of the characteristic (P) of the blood at a first and second point of the intracorporeal blood circulation path and the blood flow rate (q_(a), q_(f), q_(v)) flowing between the first and second points. 